HRP960285A2 - Oxaindene derivatives and a process for preparing thereof - Google Patents
Oxaindene derivatives and a process for preparing thereof Download PDFInfo
- Publication number
- HRP960285A2 HRP960285A2 HRP9501888A HRP960285A HRP960285A2 HR P960285 A2 HRP960285 A2 HR P960285A2 HR P9501888 A HRP9501888 A HR P9501888A HR P960285 A HRP960285 A HR P960285A HR P960285 A2 HRP960285 A2 HR P960285A2
- Authority
- HR
- Croatia
- Prior art keywords
- general formula
- acid
- hydrogen
- variant
- compound
- Prior art date
Links
- 238000004519 manufacturing process Methods 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims description 53
- 239000000203 mixture Substances 0.000 claims description 40
- 229910052739 hydrogen Inorganic materials 0.000 claims description 35
- 239000002904 solvent Substances 0.000 claims description 33
- 239000001257 hydrogen Substances 0.000 claims description 31
- 239000002253 acid Substances 0.000 claims description 29
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims description 24
- 238000000034 method Methods 0.000 claims description 22
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 claims description 21
- 239000005977 Ethylene Substances 0.000 claims description 21
- 125000005678 ethenylene group Chemical group [H]C([*:1])=C([H])[*:2] 0.000 claims description 20
- 238000006243 chemical reaction Methods 0.000 claims description 19
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 18
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 16
- 125000000217 alkyl group Chemical group 0.000 claims description 15
- 239000003054 catalyst Substances 0.000 claims description 15
- 125000003545 alkoxy group Chemical group 0.000 claims description 11
- 150000003839 salts Chemical class 0.000 claims description 11
- 229910052763 palladium Inorganic materials 0.000 claims description 8
- 230000010933 acylation Effects 0.000 claims description 7
- 238000005917 acylation reaction Methods 0.000 claims description 7
- 230000003197 catalytic effect Effects 0.000 claims description 7
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 7
- 230000029936 alkylation Effects 0.000 claims description 6
- 238000005804 alkylation reaction Methods 0.000 claims description 6
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 6
- MIOPJNTWMNEORI-GMSGAONNSA-N (S)-camphorsulfonic acid Chemical compound C1C[C@@]2(CS(O)(=O)=O)C(=O)C[C@@H]1C2(C)C MIOPJNTWMNEORI-GMSGAONNSA-N 0.000 claims description 5
- 239000000010 aprotic solvent Substances 0.000 claims description 5
- 238000009903 catalytic hydrogenation reaction Methods 0.000 claims description 5
- 201000010099 disease Diseases 0.000 claims description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 5
- 230000008569 process Effects 0.000 claims description 5
- 239000007787 solid Substances 0.000 claims description 5
- 125000002252 acyl group Chemical group 0.000 claims description 4
- 208000026935 allergic disease Diseases 0.000 claims description 4
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 claims description 4
- 229940092714 benzenesulfonic acid Drugs 0.000 claims description 4
- 208000012659 Joint disease Diseases 0.000 claims description 3
- 239000013543 active substance Substances 0.000 claims description 3
- 208000006673 asthma Diseases 0.000 claims description 3
- 150000001925 cycloalkenes Chemical class 0.000 claims description 3
- 125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 claims description 3
- 238000005984 hydrogenation reaction Methods 0.000 claims description 3
- 239000007788 liquid Substances 0.000 claims description 3
- 230000003266 anti-allergic effect Effects 0.000 claims description 2
- 230000001088 anti-asthma Effects 0.000 claims description 2
- 230000000767 anti-ulcer Effects 0.000 claims description 2
- 239000000924 antiasthmatic agent Substances 0.000 claims description 2
- 150000004945 aromatic hydrocarbons Chemical class 0.000 claims description 2
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 125000002757 morpholinyl group Chemical group 0.000 claims description 2
- 229910052757 nitrogen Inorganic materials 0.000 claims description 2
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 2
- 125000005936 piperidyl group Chemical group 0.000 claims description 2
- 239000002798 polar solvent Substances 0.000 claims description 2
- 208000017520 skin disease Diseases 0.000 claims description 2
- 238000013519 translation Methods 0.000 claims description 2
- 125000000687 hydroquinonyl group Chemical class C1(O)=C(C=C(O)C=C1)* 0.000 claims 2
- 208000010643 digestive system disease Diseases 0.000 claims 1
- 210000005095 gastrointestinal system Anatomy 0.000 claims 1
- 208000018685 gastrointestinal system disease Diseases 0.000 claims 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 55
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 54
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 52
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 51
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 51
- 239000000047 product Substances 0.000 description 39
- 239000000243 solution Substances 0.000 description 39
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 36
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 30
- 238000005160 1H NMR spectroscopy Methods 0.000 description 29
- 125000003118 aryl group Chemical group 0.000 description 29
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 21
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 18
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 18
- 239000011541 reaction mixture Substances 0.000 description 16
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 14
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 14
- YZXBAPSDXZZRGB-DOFZRALJSA-N arachidonic acid Chemical compound CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC(O)=O YZXBAPSDXZZRGB-DOFZRALJSA-N 0.000 description 14
- 238000004440 column chromatography Methods 0.000 description 14
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 12
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 11
- 235000019441 ethanol Nutrition 0.000 description 11
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 10
- 230000000694 effects Effects 0.000 description 10
- 150000002431 hydrogen Chemical class 0.000 description 10
- -1 methoxy, ethoxy, propoxy, isopropoxy Chemical group 0.000 description 10
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 9
- 102000004190 Enzymes Human genes 0.000 description 8
- 108090000790 Enzymes Proteins 0.000 description 8
- 239000000126 substance Substances 0.000 description 8
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 7
- 241001465754 Metazoa Species 0.000 description 7
- 229940114079 arachidonic acid Drugs 0.000 description 7
- 235000021342 arachidonic acid Nutrition 0.000 description 7
- MIOPJNTWMNEORI-UHFFFAOYSA-N camphorsulfonic acid Chemical compound C1CC2(CS(O)(=O)=O)C(=O)CC1C2(C)C MIOPJNTWMNEORI-UHFFFAOYSA-N 0.000 description 7
- 239000013078 crystal Substances 0.000 description 7
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 7
- 239000000725 suspension Substances 0.000 description 7
- AUFZRCJENRSRLY-UHFFFAOYSA-N 2,3,5-trimethylhydroquinone Chemical compound CC1=CC(O)=C(C)C(C)=C1O AUFZRCJENRSRLY-UHFFFAOYSA-N 0.000 description 6
- BXJGUBZTZWCMEX-UHFFFAOYSA-N 2,3-dimethylbenzene-1,4-diol Chemical compound CC1=C(C)C(O)=CC=C1O BXJGUBZTZWCMEX-UHFFFAOYSA-N 0.000 description 6
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
- 239000000706 filtrate Substances 0.000 description 6
- 239000012312 sodium hydride Substances 0.000 description 6
- 229910000104 sodium hydride Inorganic materials 0.000 description 6
- 239000011230 binding agent Substances 0.000 description 5
- 238000002474 experimental method Methods 0.000 description 5
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 5
- 235000019341 magnesium sulphate Nutrition 0.000 description 5
- DQWWMQBLEGWFHR-HTAZZLAQSA-N (5S,6E,8Z,11Z,14Z)-5-Hydroxy-6,8,11,14-eicosatetraenoic acid Natural products CCCCCCC=C/CC=C/CC=C/C=C/C(O)CCCC(=O)O DQWWMQBLEGWFHR-HTAZZLAQSA-N 0.000 description 4
- GXAVBFNRWXCOPY-UHFFFAOYSA-N 1,4-dihydroxy-2,6-dimethoxybenzene Chemical compound COC1=CC(O)=CC(OC)=C1O GXAVBFNRWXCOPY-UHFFFAOYSA-N 0.000 description 4
- 150000005208 1,4-dihydroxybenzenes Chemical class 0.000 description 4
- KGIJOOYOSFUGPC-MSFIICATSA-N 5-Hydroxyeicosatetraenoic acid Chemical compound CCCCCC=CCC=CCC=C\C=C\[C@@H](O)CCCC(O)=O KGIJOOYOSFUGPC-MSFIICATSA-N 0.000 description 4
- 241000699670 Mus sp. Species 0.000 description 4
- 150000007513 acids Chemical class 0.000 description 4
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 4
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 4
- MGNZXYYWBUKAII-UHFFFAOYSA-N cyclohexa-1,3-diene Chemical compound C1CC=CC=C1 MGNZXYYWBUKAII-UHFFFAOYSA-N 0.000 description 4
- IGRLIBJHDBWKNA-UHFFFAOYSA-N cyclopent-4-ene-1,3-diol Chemical compound OC1CC(O)C=C1 IGRLIBJHDBWKNA-UHFFFAOYSA-N 0.000 description 4
- 239000007789 gas Substances 0.000 description 4
- 210000000224 granular leucocyte Anatomy 0.000 description 4
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 4
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 4
- 239000003112 inhibitor Substances 0.000 description 4
- VNYSSYRCGWBHLG-AMOLWHMGSA-N leukotriene B4 Chemical compound CCCCC\C=C/C[C@@H](O)\C=C\C=C\C=C/[C@@H](O)CCCC(O)=O VNYSSYRCGWBHLG-AMOLWHMGSA-N 0.000 description 4
- 125000003386 piperidinyl group Chemical group 0.000 description 4
- 239000012429 reaction media Substances 0.000 description 4
- IGRLIBJHDBWKNA-SYDPRGILSA-N (1r,3s)-cyclopent-4-ene-1,3-diol Chemical compound O[C@H]1C[C@@H](O)C=C1 IGRLIBJHDBWKNA-SYDPRGILSA-N 0.000 description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- 102000001381 Arachidonate 5-Lipoxygenase Human genes 0.000 description 3
- 108010093579 Arachidonate 5-lipoxygenase Proteins 0.000 description 3
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 239000003513 alkali Substances 0.000 description 3
- PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 description 3
- 125000004432 carbon atom Chemical group C* 0.000 description 3
- 210000004027 cell Anatomy 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- ZSWFCLXCOIISFI-UHFFFAOYSA-N cyclopentadiene Chemical compound C1C=CC=C1 ZSWFCLXCOIISFI-UHFFFAOYSA-N 0.000 description 3
- 229960004132 diethyl ether Drugs 0.000 description 3
- 239000012259 ether extract Substances 0.000 description 3
- 150000004820 halides Chemical class 0.000 description 3
- 238000011534 incubation Methods 0.000 description 3
- 210000000265 leukocyte Anatomy 0.000 description 3
- 239000012074 organic phase Substances 0.000 description 3
- 239000002244 precipitate Substances 0.000 description 3
- 239000003981 vehicle Substances 0.000 description 3
- GWYPDXLJACEENP-UHFFFAOYSA-N 1,3-cycloheptadiene Chemical compound C1CC=CC=CC1 GWYPDXLJACEENP-UHFFFAOYSA-N 0.000 description 2
- VFLQQZCRHPIGJU-UHFFFAOYSA-N 1-(2-chloroethyl)piperidine;hydron;chloride Chemical compound Cl.ClCCN1CCCCC1 VFLQQZCRHPIGJU-UHFFFAOYSA-N 0.000 description 2
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 2
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 2
- YMDNODNLFSHHCV-UHFFFAOYSA-N 2-chloro-n,n-diethylethanamine Chemical compound CCN(CC)CCCl YMDNODNLFSHHCV-UHFFFAOYSA-N 0.000 description 2
- LAQYHRQFABOIFD-UHFFFAOYSA-N 2-methoxyhydroquinone Chemical compound COC1=CC(O)=CC=C1O LAQYHRQFABOIFD-UHFFFAOYSA-N 0.000 description 2
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 2
- HVBSAKJJOYLTQU-UHFFFAOYSA-N 4-aminobenzenesulfonic acid Chemical compound NC1=CC=C(S(O)(=O)=O)C=C1 HVBSAKJJOYLTQU-UHFFFAOYSA-N 0.000 description 2
- HIYAVKIYRIFSCZ-CYEMHPAKSA-N 5-(methylamino)-2-[[(2S,3R,5R,6S,8R,9R)-3,5,9-trimethyl-2-[(2S)-1-oxo-1-(1H-pyrrol-2-yl)propan-2-yl]-1,7-dioxaspiro[5.5]undecan-8-yl]methyl]-1,3-benzoxazole-4-carboxylic acid Chemical compound O=C([C@@H](C)[C@H]1O[C@@]2([C@@H](C[C@H]1C)C)O[C@@H]([C@@H](CC2)C)CC=1OC2=CC=C(C(=C2N=1)C(O)=O)NC)C1=CC=CN1 HIYAVKIYRIFSCZ-CYEMHPAKSA-N 0.000 description 2
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 2
- 208000001953 Hypotension Diseases 0.000 description 2
- 239000000867 Lipoxygenase Inhibitor Substances 0.000 description 2
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
- 238000011785 NMRI mouse Methods 0.000 description 2
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 150000008065 acid anhydrides Chemical class 0.000 description 2
- 239000008346 aqueous phase Substances 0.000 description 2
- 239000012300 argon atmosphere Substances 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000001110 calcium chloride Substances 0.000 description 2
- 235000011148 calcium chloride Nutrition 0.000 description 2
- 229910001628 calcium chloride Inorganic materials 0.000 description 2
- HGCIXCUEYOPUTN-UHFFFAOYSA-N cis-cyclohexene Natural products C1CCC=CC1 HGCIXCUEYOPUTN-UHFFFAOYSA-N 0.000 description 2
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 210000005069 ears Anatomy 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 210000001035 gastrointestinal tract Anatomy 0.000 description 2
- KDCIHNCMPUBDKT-UHFFFAOYSA-N hexane;propan-2-one Chemical compound CC(C)=O.CCCCCC KDCIHNCMPUBDKT-UHFFFAOYSA-N 0.000 description 2
- 208000021822 hypotensive Diseases 0.000 description 2
- 230000001077 hypotensive effect Effects 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 239000012299 nitrogen atmosphere Substances 0.000 description 2
- HCZKYJDFEPMADG-UHFFFAOYSA-N nordihydroguaiaretic acid Chemical compound C=1C=C(O)C(O)=CC=1CC(C)C(C)CC1=CC=C(O)C(O)=C1 HCZKYJDFEPMADG-UHFFFAOYSA-N 0.000 description 2
- 239000003921 oil Substances 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 125000003232 p-nitrobenzoyl group Chemical group [N+](=O)([O-])C1=CC=C(C(=O)*)C=C1 0.000 description 2
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 2
- CMCWWLVWPDLCRM-UHFFFAOYSA-N phenidone Chemical compound N1C(=O)CCN1C1=CC=CC=C1 CMCWWLVWPDLCRM-UHFFFAOYSA-N 0.000 description 2
- 238000003127 radioimmunoassay Methods 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- 238000005303 weighing Methods 0.000 description 2
- 239000008096 xylene Substances 0.000 description 2
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
- IANQTJSKSUMEQM-UHFFFAOYSA-N 1-benzofuran Chemical class C1=CC=C2OC=CC2=C1 IANQTJSKSUMEQM-UHFFFAOYSA-N 0.000 description 1
- RMMPZDDLWLALLJ-UHFFFAOYSA-N 2,5-dimethoxy-1,4-benzoquinone Natural products COC1=CC(=O)C(OC)=CC1=O RMMPZDDLWLALLJ-UHFFFAOYSA-N 0.000 description 1
- GLJCPHKWYYCHCQ-UHFFFAOYSA-N 2,5-dimethoxybenzene-1,4-diol Chemical compound COC1=CC(O)=C(OC)C=C1O GLJCPHKWYYCHCQ-UHFFFAOYSA-N 0.000 description 1
- KNLOVRSDDIMPEF-UHFFFAOYSA-N 2,5-dipropoxybenzene-1,4-diol Chemical compound CCCOC1=CC(O)=C(OCCC)C=C1O KNLOVRSDDIMPEF-UHFFFAOYSA-N 0.000 description 1
- HVAUUPRFYPCOCA-AREMUKBSSA-N 2-O-acetyl-1-O-hexadecyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCCOC[C@@H](OC(C)=O)COP([O-])(=O)OCC[N+](C)(C)C HVAUUPRFYPCOCA-AREMUKBSSA-N 0.000 description 1
- BUHYMJLFRZAFBF-UHFFFAOYSA-N 3,4,5-trimethoxybenzoyl chloride Chemical compound COC1=CC(C(Cl)=O)=CC(OC)=C1OC BUHYMJLFRZAFBF-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- NBJHDLKSWUDGJG-UHFFFAOYSA-N 4-(2-chloroethyl)morpholin-4-ium;chloride Chemical compound Cl.ClCCN1CCOCC1 NBJHDLKSWUDGJG-UHFFFAOYSA-N 0.000 description 1
- HLLSOEKIMZEGFV-UHFFFAOYSA-N 4-(dibutylsulfamoyl)benzoic acid Chemical compound CCCCN(CCCC)S(=O)(=O)C1=CC=C(C(O)=O)C=C1 HLLSOEKIMZEGFV-UHFFFAOYSA-N 0.000 description 1
- WUBBRNOQWQTFEX-UHFFFAOYSA-N 4-aminosalicylic acid Chemical compound NC1=CC=C(C(O)=O)C(O)=C1 WUBBRNOQWQTFEX-UHFFFAOYSA-N 0.000 description 1
- WNWVKZTYMQWFHE-UHFFFAOYSA-N 4-ethylmorpholine Chemical group [CH2]CN1CCOCC1 WNWVKZTYMQWFHE-UHFFFAOYSA-N 0.000 description 1
- SKDHHIUENRGTHK-UHFFFAOYSA-N 4-nitrobenzoyl chloride Chemical compound [O-][N+](=O)C1=CC=C(C(Cl)=O)C=C1 SKDHHIUENRGTHK-UHFFFAOYSA-N 0.000 description 1
- 229940124125 5 Lipoxygenase inhibitor Drugs 0.000 description 1
- JNUUNUQHXIOFDA-UHFFFAOYSA-N 5-hydroperoxyicosa-6,8,11,14-tetraenoic acid Chemical compound CCCCCC=CCC=CCC=CC=CC(OO)CCCC(O)=O JNUUNUQHXIOFDA-UHFFFAOYSA-N 0.000 description 1
- 206010002199 Anaphylactic shock Diseases 0.000 description 1
- 102000011730 Arachidonate 12-Lipoxygenase Human genes 0.000 description 1
- 108010076676 Arachidonate 12-lipoxygenase Proteins 0.000 description 1
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- 241000700199 Cavia porcellus Species 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 206010009900 Colitis ulcerative Diseases 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 240000001307 Myosotis scorpioides Species 0.000 description 1
- 206010030113 Oedema Diseases 0.000 description 1
- 208000005141 Otitis Diseases 0.000 description 1
- 108010003541 Platelet Activating Factor Proteins 0.000 description 1
- 102000004005 Prostaglandin-endoperoxide synthases Human genes 0.000 description 1
- 108090000459 Prostaglandin-endoperoxide synthases Proteins 0.000 description 1
- 201000004681 Psoriasis Diseases 0.000 description 1
- 206010039085 Rhinitis allergic Diseases 0.000 description 1
- 208000028990 Skin injury Diseases 0.000 description 1
- 208000025865 Ulcer Diseases 0.000 description 1
- 201000006704 Ulcerative Colitis Diseases 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 150000001338 aliphatic hydrocarbons Chemical class 0.000 description 1
- 229910001854 alkali hydroxide Inorganic materials 0.000 description 1
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 1
- 150000004703 alkoxides Chemical class 0.000 description 1
- 201000010105 allergic rhinitis Diseases 0.000 description 1
- 230000007815 allergy Effects 0.000 description 1
- 229960004909 aminosalicylic acid Drugs 0.000 description 1
- BFNBIHQBYMNNAN-UHFFFAOYSA-N ammonium sulfate Chemical compound N.N.OS(O)(=O)=O BFNBIHQBYMNNAN-UHFFFAOYSA-N 0.000 description 1
- 229910052921 ammonium sulfate Inorganic materials 0.000 description 1
- 235000011130 ammonium sulphate Nutrition 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 208000003455 anaphylaxis Diseases 0.000 description 1
- 125000004063 butyryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- HIYAVKIYRIFSCZ-UHFFFAOYSA-N calcium ionophore A23187 Natural products N=1C2=C(C(O)=O)C(NC)=CC=C2OC=1CC(C(CC1)C)OC1(C(CC1C)C)OC1C(C)C(=O)C1=CC=CN1 HIYAVKIYRIFSCZ-UHFFFAOYSA-N 0.000 description 1
- 150000001718 carbodiimides Chemical class 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 150000004649 carbonic acid derivatives Chemical class 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 150000001805 chlorine compounds Chemical class 0.000 description 1
- 239000000812 cholinergic antagonist Substances 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 239000012230 colorless oil Substances 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- FDODVZVWGKVMBO-UHFFFAOYSA-N cyclohex-2-ene-1,4-diol Chemical compound OC1CCC(O)C=C1 FDODVZVWGKVMBO-UHFFFAOYSA-N 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 210000000172 cytosol Anatomy 0.000 description 1
- KPSZWAJWFMFMFF-UHFFFAOYSA-N delta-Hexylen-alpha-carbonsaeure Natural products CC=CCCCC(O)=O KPSZWAJWFMFMFF-UHFFFAOYSA-N 0.000 description 1
- KPSZWAJWFMFMFF-NSCUHMNNSA-N delta-heptenoic acid Chemical compound C\C=C\CCCC(O)=O KPSZWAJWFMFMFF-NSCUHMNNSA-N 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 239000002532 enzyme inhibitor Substances 0.000 description 1
- 229940125532 enzyme inhibitor Drugs 0.000 description 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
- 229940052303 ethers for general anesthesia Drugs 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 235000019256 formaldehyde Nutrition 0.000 description 1
- 238000005194 fractionation Methods 0.000 description 1
- ZZUFCTLCJUWOSV-UHFFFAOYSA-N furosemide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC(C(O)=O)=C1NCC1=CC=CO1 ZZUFCTLCJUWOSV-UHFFFAOYSA-N 0.000 description 1
- 150000008282 halocarbons Chemical class 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- UWYVPFMHMJIBHE-OWOJBTEDSA-N hydroxymaleic acid group Chemical group O/C(/C(=O)O)=C/C(=O)O UWYVPFMHMJIBHE-OWOJBTEDSA-N 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000028709 inflammatory response Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 150000002617 leukotrienes Chemical class 0.000 description 1
- 238000012417 linear regression Methods 0.000 description 1
- 239000006166 lysate Substances 0.000 description 1
- 229910001629 magnesium chloride Inorganic materials 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical compound [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 239000010413 mother solution Substances 0.000 description 1
- IUSXYVRFJVAVOB-UHFFFAOYSA-N n-(2-chloroethyl)-n-propan-2-ylpropan-2-amine;hydron;chloride Chemical compound Cl.CC(C)N(C(C)C)CCCl IUSXYVRFJVAVOB-UHFFFAOYSA-N 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 239000012053 oil suspension Substances 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 229940094443 oxytocics prostaglandins Drugs 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- 150000003180 prostaglandins Chemical class 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 206010039073 rheumatoid arthritis Diseases 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 230000002048 spasmolytic effect Effects 0.000 description 1
- 238000002798 spectrophotometry method Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 229950000244 sulfanilic acid Drugs 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 231100000397 ulcer Toxicity 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D307/78—Benzo [b] furans; Hydrogenated benzo [b] furans
- C07D307/79—Benzo [b] furans; Hydrogenated benzo [b] furans with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the hetero ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D307/91—Dibenzofurans; Hydrogenated dibenzofurans
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/34—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/02—Drugs for disorders of the urinary system of urine or of the urinary tract, e.g. urine acidifiers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D307/93—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems condensed with a ring other than six-membered
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Urology & Nephrology (AREA)
- Dermatology (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Immunology (AREA)
- Endocrinology (AREA)
- Reproductive Health (AREA)
- Pulmonology (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Furan Compounds (AREA)
- Steroid Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| HU9501888A HU221322B1 (en) | 1995-06-27 | 1995-06-27 | 2,3 dihydro benzo[b]furan derivatives, process for producing them and medicament containing them |
| HU9501887A HU221321B1 (en) | 1995-06-27 | 1995-06-27 | 2,3 dihydro-benzo[b]furan derivatives, process for producing them and medicines containing the same |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| HRP960285A2 true HRP960285A2 (en) | 1997-10-31 |
Family
ID=26318226
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HRP9501888A HRP960285A2 (en) | 1995-06-27 | 1996-06-17 | Oxaindene derivatives and a process for preparing thereof |
Country Status (13)
| Country | Link |
|---|---|
| US (1) | US5716986A (cs) |
| EP (1) | EP0751137A1 (cs) |
| JP (1) | JPH0912566A (cs) |
| KR (1) | KR970001340A (cs) |
| CA (1) | CA2180029A1 (cs) |
| CZ (1) | CZ168896A3 (cs) |
| EA (1) | EA000025B1 (cs) |
| FR (1) | FR2736052A1 (cs) |
| GB (1) | GB2302691B (cs) |
| HR (1) | HRP960285A2 (cs) |
| IT (1) | IT1284080B1 (cs) |
| PL (1) | PL314947A1 (cs) |
| SK (1) | SK79396A3 (cs) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2252378A1 (en) * | 1997-02-21 | 1998-08-27 | Hiroshi Nagase | Process for producing optically active isomers of tricyclic compounds |
| DE10227188A1 (de) * | 2002-06-18 | 2004-01-08 | Basf Drucksysteme Gmbh | Verfahren zur Herstellung von Flexodruckformen mittels Laser-Direktgravur |
Family Cites Families (19)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3574627A (en) * | 1969-02-06 | 1971-04-13 | Eastman Kodak Co | Color photographic elements |
| CH574433A5 (cs) * | 1971-03-26 | 1976-04-15 | Hoffmann La Roche | |
| JPS589114B2 (ja) * | 1977-06-30 | 1983-02-18 | 大塚製薬株式会社 | セスキテルペン類縁体、その製造法及び腎炎治療剤 |
| SU869278A1 (ru) * | 1980-03-21 | 1986-12-15 | Научно-исследовательский институт фармакологии АМН СССР | Производные 1-амино-3-(1,2,3,4-тетрагидро-или 1,2,3,4,4 @ ,9 @ -гексагидродибензофуранил-8-окси)-пропанолов-2,обладающие @ -адреноблокирующим,гипотензивным,спазмолитическим,нейротропно-депримирующим и бронхолитическим свойствами |
| FR2482966A1 (fr) * | 1980-05-23 | 1981-11-27 | Cerm Cent Europ Rech Mauvernay | 1, 2, 3, 4, 4a, 9b, -hexahydro 4-amino dibenzofurannes, leur procede de preparation et leur application en therapeutique |
| FI74950C (fi) * | 1980-09-18 | 1988-04-11 | Ucb Sa | Foerfarande foer framstaellning av terapeutiskt aktiva 2-/4-(difenylmetylen)-1-piperidinyl-aettiksyror. |
| JPS58124778A (ja) * | 1982-01-20 | 1983-07-25 | Toray Ind Inc | ５，６，７−トリノル−４，８−インタ−ｍ−フエニレンＰＧＩ↓２誘導体 |
| ES8602818A1 (es) * | 1983-10-31 | 1985-12-01 | Merck Frosst Canada Inc | Una composicion farmaceutica |
| SU1180368A1 (ru) * | 1984-03-26 | 1985-09-23 | Киевский Ордена Ленина Политехнический Институт Им.50-Летия Великой Октябрьской Социалистической Революции | Способ получени 2,3-циклоалкано-2,3-дигидробензофуранов |
| US4742057A (en) * | 1985-12-05 | 1988-05-03 | Fujisawa Pharmaceutical Co., Ltd. | Antiallergic thiazole compounds |
| FR2621917B1 (fr) * | 1987-10-16 | 1990-03-02 | Roussel Uclaf | Nouveaux derives du 6, 7, 8, 9 tetrahydro 1-dibenzofurannol, leur procede de preparation et leur application comme medicaments |
| US4822811A (en) * | 1987-11-13 | 1989-04-18 | Abbott Laboratories | Carbazole lipoxygenase inhibiting compounds, compositions and use |
| US4959485A (en) * | 1988-04-27 | 1990-09-25 | Rorer Pharmaceutical Corporation | Hexahydrodibenzofuran carboxylic acid derivatives |
| US4975457A (en) * | 1989-09-25 | 1990-12-04 | Merck & Co., Inc. | Trans 2,3-disubstituted-2,3-dihydro-5-hydroxy-benzofurans as inhibitors of leukotriene biosynthesis |
| US4978679A (en) * | 1989-09-25 | 1990-12-18 | Merck & Co., Inc. | 6- and/or 7-substituted-1,2,3,4,4A,9B-hexahydro-8-hydroxydibenzofuran-3-ols as inhibitors of leukotriene biosynthesis |
| JPH03148217A (ja) * | 1989-11-02 | 1991-06-25 | Terumo Corp | フエノキシプロピルアミン誘導体またはその塩ならびにこれらを含有する抗潰瘍剤 |
| US5278323A (en) * | 1993-04-30 | 1994-01-11 | Rhone-Poulenc Rorer Pharmaceuticals Inc. | Process for preparing chiral dibenzofurans via intramolecular heck reaction |
| WO1995002403A1 (en) * | 1993-07-14 | 1995-01-26 | Smithkline Beecham Corporation | 5-lipoxygenase inhibitors |
| US5401769A (en) * | 1994-02-02 | 1995-03-28 | American Home Products Corporation | Dibenzofuranyl N-alkyl carbamates |
-
1996
- 1996-06-10 CZ CZ961688A patent/CZ168896A3/cs unknown
- 1996-06-17 HR HRP9501888A patent/HRP960285A2/hr not_active Application Discontinuation
- 1996-06-18 SK SK793-96A patent/SK79396A3/sk unknown
- 1996-06-25 PL PL96314947A patent/PL314947A1/xx unknown
- 1996-06-25 EP EP96110220A patent/EP0751137A1/en not_active Withdrawn
- 1996-06-25 FR FR9607869A patent/FR2736052A1/fr active Pending
- 1996-06-26 KR KR1019960023757A patent/KR970001340A/ko not_active Withdrawn
- 1996-06-26 CA CA002180029A patent/CA2180029A1/en not_active Abandoned
- 1996-06-26 EA EA199600034A patent/EA000025B1/ru not_active IP Right Cessation
- 1996-06-26 GB GB9613370A patent/GB2302691B/en not_active Expired - Fee Related
- 1996-06-27 JP JP8167196A patent/JPH0912566A/ja active Pending
- 1996-06-27 US US08/671,515 patent/US5716986A/en not_active Expired - Fee Related
- 1996-06-27 IT IT96MI001314A patent/IT1284080B1/it active IP Right Grant
Also Published As
| Publication number | Publication date |
|---|---|
| CZ168896A3 (en) | 1997-01-15 |
| PL314947A1 (en) | 1997-01-06 |
| EA199600034A3 (ru) | 1997-03-31 |
| SK79396A3 (en) | 1997-01-08 |
| EA000025B1 (ru) | 1998-02-26 |
| GB9613370D0 (en) | 1996-08-28 |
| GB2302691B (en) | 1998-09-02 |
| GB2302691A (en) | 1997-01-29 |
| CA2180029A1 (en) | 1996-12-28 |
| ITMI961314A0 (cs) | 1996-06-27 |
| IT1284080B1 (it) | 1998-05-08 |
| KR970001340A (ko) | 1997-01-24 |
| EA199600034A2 (ru) | 1996-12-30 |
| EP0751137A1 (en) | 1997-01-02 |
| ITMI961314A1 (it) | 1997-12-27 |
| FR2736052A1 (fr) | 1997-01-03 |
| JPH0912566A (ja) | 1997-01-14 |
| US5716986A (en) | 1998-02-10 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US5604261A (en) | Arylalkyl (thio)amides | |
| CA1090795A (en) | 2-phenyl-3-aroylbenzothiophenes and their 1-oxides | |
| US3420851A (en) | Novel dibenzoxepines | |
| HK22484A (en) | Enzyme inhibitory phthalazin-4-ylacetic acid derivatives, pharmaceutical compositions thereof, and process for their manufacture | |
| US5451600A (en) | Substituted tetrahydrobenzopyrrolylfuranoic acid derivatives as phospholipase A2 inhibitors | |
| US5780512A (en) | Alkylated (hetero) cyclic compounds | |
| US5063243A (en) | Derivative of caffeic acid and pharmaceutical composition containing the same | |
| Saccomano et al. | Calcium-independent phosphodiesterase inhibitors as putative antidepressants:[3-(bicycloalkyloxy)-4-methoxyphenyl-2-imidazolidinones | |
| US5254590A (en) | Acylaminophenol compounds | |
| HU208432B (en) | Process for producing 2-/amino-alkyl/-5-/aryl-alkyl/-1,3-dioxane derivatives and pharmaceutical compositions containing them as active components | |
| HRP960285A2 (en) | Oxaindene derivatives and a process for preparing thereof | |
| US4264626A (en) | Benzo-bicyclonoene-derivatives as anorectants and to treat depression | |
| PL195667B1 (pl) | Nowe związki cykliczne zawierające łańcuch cyklopropylenowy, sposób ich wytwarzania, kompozycje farmaceutyczne zawierające te związki i ich zastosowanie | |
| CA2075632C (en) | Chromene derivatives, their production and use | |
| US5057514A (en) | Compounds effective as cerebral schemia treating agents | |
| US4622336A (en) | 3,3-dialkyl-and 3,3-alkylene-indoline derivatives, processes for their production and pharmaceutical compositions comprising them | |
| US5179092A (en) | Compound effective as cerebral insufficiency improver | |
| FR2600647A1 (fr) | Derives de la glycine | |
| US5288752A (en) | Compound effective as cerebral insufficiency improver | |
| CA1078834A (en) | Antifertility compounds | |
| CA1326675C (fr) | Derives trieniques de structure chromenique, leurs procedes de preparation et les compositions pharmaceutiques qui les contiennent | |
| US3513201A (en) | Process for preparing 5-(3-alkylaminopropyl)-5h-dibenzo(a,d)cycloheptenes | |
| US4156694A (en) | Benzobicyclononene derivatives | |
| US5103023A (en) | Biphenyl derivatives, process for preparing the same and intermediates therefor | |
| US4804684A (en) | Symmetrical O-substituted dioximes of benzo-fused β-diketocyclo-alkylenes, the processes for their preparation and their application as drugs |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A1OB | Publication of a patent application | ||
| AIPI | Request for the grant of a patent on the basis of a substantive examination of a patent application | ||
| OBST | Application withdrawn |